Introduction: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer’s disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. Methods: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. Results: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology. Conclusion: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.

The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.

Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, and the treatment effects are usually unsatisfactory. Vinorelbine (VRB) is extensively used in cancer treatment, but it has some disadvantages when used alone. PEGylated liposomes have been extensively used as a delivery carrier for antitumor drugs via prolonging the circulation time in the blood. Purpose: The nanostructured liposomes were designed and prepared for treating NSCLC. Methods: In the liposomes, PEG was modified on the liposomal surface, DC-Chol was used as cationic materials, and VRB plus quinacrine were encapsulated in an aqueous core of the liposomes as an antitumor drug and an apoptosis-inducing agent, respectively. Evaluations were performed on A549 cells, tubular network formations and xenografts of the A549 cells. Results: The PEGylated drugs-loaded cationic liposomes could significantly enhance cellular uptake and selectively accumulate in A549 cells, thus leading to show strongest antitumor efficacy to tumor cells and to tumor-bearing mice. Action mechanisms showed that the enhanced efficacy in treating NSCLC was related to activate caspase 9 and caspase 3, to activate Bax and P53, and to suppress Bcl-2 and Mcl-1. Conclusion: The PEGylated VRB plus quinacrine cationic liposomes showed a potential strategy for treating NSCLC.

Ginkgolide B (GB), which has been demonstrated as the most efficacious naturally occurring platelet-activating factor (PAF) antagonist, is extensively utilized for the management of cardiovascular and cerebrovascular ailments. Nevertheless, its limited oral bioavailability is hindered by its low solubility in gastric acid and inadequate stability in intestinal fluid, thereby constraining its practical application. This study aimed to develop GB nanocrystals (GB-NCs) and GB nanocrystals self-stabilized Pickering nano-emulsion (GB-NSSPNE) using a miniaturized wet bead milling method. Comparative evaluations were conducted in vivo and in vitro to assess their effectiveness. The findings revealed that GB-NSSPNE, with its intact nanoparticle slow release and absorption, was more effective in enhancing the oral bioavailability of GB compared to the rapid release and absorption of GB-NCs. This finding suggests a potential novel strategy for the oral delivery of GB.

Although hyperlipidemia is a key factor in cardiovascular disease, there are limited safe and effective therapies for disorders of lipid metabolism. This study investigated the therapeutic potential of Ginkgolide B (GB), a bioactive component of Ginkgo biloba leaves, in ameliorating hyperlipidemia and explored its underlying mechanisms. Utilizing a high-fat diet-induced hyperlipidemic rat model and lipidomics analysis, the study showed that GB significantly decreased serum total cholesterol, triglyceride, and low-density lipoprotein levels. Lipidomics revealed that GB reversed dysregulated sphingolipid metabolism, notably decreasing ceramides levels and increasing sphingomyelins, which are implicated in metabolic inflammation and oxidative stress. Mechanistically, GB activated PPARα, thereby enhancing fatty acid oxidation and upregulating the Nrf2 pathway to mitigate oxidative damage. These dual effects were validated in vitro using HepG2 cells, where GB reduced lipid accumulation and improved antioxidant defenses. Overall, these findings highlight GB as a promising therapeutic agent for hyperlipidemia by restoring sphingolipid homeostasis and targeting the interplay between lipid metabolism and oxidative stress.